Process for the preparation of 3-aminophenyl 2-hydroxy-ethyl sulphone

ABSTRACT

3-Aminophenyl 2-hydroxyethyl sulphone (I) can be prepared in a high yield and purity by treating 2-chloro-5-nitrophenyl 2-hydroxyethyl sulphone (II) or 4-chloro-3-nitrophenyl 2-hydroxyethyl sulphone (III) with hydrogen in the presence of hydrogenation catalysts in an aqueous or aqueous organic medium. (II) is obtained by reducing 2-chloro-5-nitrobenzenesulphochloride with sodium sulphite and subsequently reacting the product with ethylene oxide.

The present invention relates to a process for the preparation of thesulphone of the formula ##STR1## which is characterized in that anitrosulphone of the formula ##STR2## or a mixture of II and III istreated with hydrogen in the presence of hydrogenation catalysts.

The reaction is preferably carried out in an aqueous or aqueous organicmedium, if appropriate in the presence of inert dispersants oremulsifiers.

Organic solvents suitable for this reaction are, in particular,water-miscible solvents, such as low-molecular aliphatic alcohols andethers thereof, and also ethers such as dioxane and tetrahydrofuran.They are employed, if appropriate, in amounts of about 5 to 25% byweight.

The reaction is carried out at temperatures of about 40°-120° C.,preferably 60°-80° C.

During the reaction the pH should be within the range from 5 to 8,preferably in the neutral range. This can be achieved by adding buffersubstances, in particular phosphates, such as mixtures of primary,secondary and tertiary alkali metal phosphates, borates, acetates oralkali metal bicarbonates or alkali metal carbonates.

The required amount of buffer substances can readily be determined bypreliminary tests. In the case of the alkali metal bicarbonates, it isappropriate to use equimolar amounts, relative to (II) or (III),respectively.

Examples of suitable hydrogenation catalysts are catalysts which consistof metals and/or compounds of elements of the eighth subgroup of thePeriodic System of the elements according to Mendelyeev, or whichcontain the latter. The metals ruthenium, rhodium, palladium, platinum,cobalt and nickel and compounds thereof are preferred in this regard.The metal compounds can be, for example, oxides, hydroxides and/orhydrated oxides. The metals copper, vanadium, molybdenum, chromiumand/or manganese and also compounds of these metals can be present inaddition.

The hydrogenation catalysts can consist solely or mainly of substanceswhich transfer hydrogen, but these catalysts can also be deposited onsupporting materials. The following are examples of suitable supportingmaterials for the hydrogen-transferring substances: inorganic materialssuch as kieselguhr, silica, aluminium oxides, alkali metal and alkalineearth metal silicates, aluminium silicates, montmorillonite, zeolites,spinels, dolomite, kaolin, magnesium silicates, zirconium oxide, zincoxide, calcium carbonate, silicon carbide, aluminium phosphate, boronphosphate, asbestos, active charcoal or barium sulphate, and alsoorganic materials, for example naturally occurring or syntheticcompounds of high molecular weight, such as silk, polyamides,polystyrenes, cellulose or polyurethanes. Inorganic supporting materialsare preferred. The supporting material can be present, for example, inthe form of spheres, extrudates, threads, cylinders, polygons or in theform of powder.

Supported catalysts of this type can, in general, contain 0.5 to 50% byweight, preferably 1 to 10% by weight, of the hydrogen-transferringsubstance, relative to the total weight of the supported catalyst. Inthis regard the hydrogen-transferring substance can be homogeneouslydistributed within the supporting material, but catalysts in which thehydrogen-transferring substance has been deposited in the outer layer oron the surface thereof are preferred. The preparation and the shaping ofcatalysts which can be used in the process according to the inventioncan be carried out in a known manner (see, for example, Houben-Weyl,Methoden der organischen Chemie ("Methods of organic chemistry"), volumeIV, 1c, part I, pages 16-26, Georg Thieme-Verlag, Stuttgart, 1980).

Preferred supported catalysts are ruthenium on charcoal, ruthenium onaluminium oxide, rhodium on charcoal, rhodium on aluminium oxide,palladium on charcoal, palladium on aluminium oxide, palladium oncalcium carbonate, palladium on barium sulphate, palladium on silica,platinum on charcoal and platinum on aluminium oxide.

Examples of preferred hydrogenation catalysts consisting solely ormainly of a hydrogen-transferring substance are oxide catalysts, such aspalladium oxide, platinum oxide, ruthenium oxide and/or rhodiumoxide/platinum oxide by Nishimura's method, and also black catalysts,such as palladium black, platinum black and rhodium black, which can beprepared by reducing corresponding metal salts or metal salt mixtureswith alkali metal hydrides, alkali metal boranates, metal alkyls,hydrazine, formaldehyde, hydrogen or more electropositive metals.

Catalysts which are particularly preferred for the process according tothe invention are palladium on charcoal, palladium on aluminium oxide,palladium on silica and palladium on calcium carbonate and also Raneynickel.

The amount of catalyst is generally about 0.1 to 10% by weight,preferably 0.1 to 5% by weight, relative to (II) or (III).

The hydrogen pressure is about 1 to 120 bar, preferably 5 to 40 bar.

The reaction time required for the process according to the inventiondepends on the reaction rate, the hydrogen partial pressure, theintensity with which the reaction mixture is mixed and the activity andconcentration of the hydrogenation catalyst. In general, the reactiontime necessary is within the range from 15 minutes up to several hours.

The catalytic activity of the hydrogenation catalysts is, in general,substantially retained when the process according to the invention iscarried out, so that these catalysts can be employed repeatedly in thecase of discontinuous procedure and can remain in use for a prolongedperiod in the case of continuous procedure.

In a simple discontinuous embodiment the process according to theinvention can, for example, be carried out as follows: an autoclavecapable of being thermostatically controlled and equipped with astirring or mixing device is charged with the (II) or (III) to beemployed, the hydrogenation catalyst and water or a water/solventmixture. Hydrogen is then injected until the desired pressure isreached, and the mixture is heated to the desired reaction temperaturewith vigourous mixing. The progress of the reaction can be followedeasily by measuring the consumption of hydrogen. Hydrogen consumedduring the reaction can subsequently be metered in continuously ordiscontinuously. Th hydrogenation is discontinued when the desiredamount of hydrogen has been taken up. The hydrogenation can bediscontinued by cooling, terminating the mixing, releasing the pressureand/or removing the hydrogen atmosphere. The reaction mixture can, forexample, be worked up by first filtering off the catalyst andconcentrating the residual reaction solution and isolating, by filteringoff with suction, the products which crystallize. The process accordingto the invention can also be carried out continuously.

The process can be carried out in one or two stages. In the two-stageprocess, the nitro group is fist reduced at about 40° C. in an aqueousmedium, and reductive dehalogenation then carried out at above 50° C.after acid-binding buffer substances have been added. It is preferableto carry out the reaction in a single stage.

The present invention also relates to a process for the preparation of(I), characterized in that 2-chloro-5-nitrobenzenesulfochloride isreacted with sodium sulphite to give 2-chloro-5-nitrobenzenesulphinicacid, the latter is then reacted with ethylene oxide to give (II) andthis is treated with hydrogen in the presence of hydrogenationcatalysts.

Compared with the previously known process for the preparation of (I),namely converting 3-nitrobenzenesulphochloride into3-nitrobenzenesulphinic acid, reacting the latter with ethylene oxideand subsequently reducing the nitro group, the process according to theinvention exhibits the surprising advantage that it affords higheryields and a smaller amount of byproducts which are difficult to remove.

(I) is a valuable intermediate product for the preparation of dyestuffs.It is employed, for example, as a diazo component in the preparation ofazo dyestuffs, in particular after being previously sulphated to givesulphatoethylsulphonylaniline.

EXAMPLE 1 Sodium 2-chloro-5-nitrobenzenesulphinate

The pH of a mixture of 1,000 g (3.8 moles) of a freshly prepared,approximately 40% strength aqueous solution of sodium bisulphite and 500g of ice is adjusted to 7.5 by means of approximately 200 ml ofconcentrated sodium hydroxide solution. The mixture is cooled to 10° C.by adding approximately 400 g of ice. 1.47 kg (3.8 moles) of2-chloro-5-nitrobenzenesulphonyl chloride in the form of a moist pasteare introduced in portions at 10°-15° C. The temperature is keptconstant by adding 1.6 kg of ice and the pH is kept constant at a valueof 7-7.5 by adding 380 ml of sodium hydroxide solution. Stirring iscontinued subsequently until there is virtually no further change in thepH. The time required for the introduction and the subsequent stirringis about 4 hours. The pH is adjusted to 8.5 and 15 g of a customaryfilter aid are added. Clarification is carried out after a short periodof further stirring, and the filter is rinsed with approximately 300 mlof water. The product is salted out with 1.3 kg of sodium chloride, themixture is stirred for a further hour and the product is separated in afilter press. 1.35 kg of moist 2-chloro-5-nitrobenzenesulphinate areisolated. Analysis by HPLC gives a purity of 58.4%, which corresponds toa yield of 85% of theory. The product contains approximately 2% of2-chloro-5-nitrobenzenesulphonate.

2-Chloro-5-nitrophenyl 2-hydroxyethyl sulphone

1,045 g (2.5 moles) of 2-chloro-5-nitrobenzenesulphinate in the form ofa 58.4% strength moist paste and 1,250 ml of water are charged to areaction vessel which has been flushed with nitrogen, and the pH isadjusted to a value between 7 and 8. The solution is heated to 60° C.under nitrogen. A total of 550 g of ethylene oxide is passed in slowly,the pH being kept meanwhile between 6 and 8 by metering in 25% strengthsulphuric acid. A total of 1.02 kg of sulphuric acid is consumed. Thereaction is complete after approximately 6-7 hours. Nitrogen is passedthrough the mixture for 1 hour at pH 7 and 85° C., and the latter isthen cooled to room temperature. After stirring for 4 hours at 20° C.,the precipitate is filtered off with suction and washed with twice 500ml of water. This gives 775 g of moist paste or, after drying at 60 70°C. in vacuo, 602 g of 2-chloro-5-nitrophenyl 2-hydroxyethyl sulphone.According to C, H and N analysis and determination of nitro groups,chlorine and sulphur, the product is 98% pure, from which the yield iscalculated to be 90.5% of theory.

3-Aminophenyl 2-hydoxyethyl sulphone

271 g (1 mole) of the above 2-chloro-6-nitrophenyl 2-hydroxyethylsulphone are stirred into 1.8 l of water in a 3 l autoclave, and 85 g ofsolid sodium bicarbonate and 1 ml of an emulsifier (polyether based onlauryl alcohol and ethylene oxide) are added. The mixture is heated to70° C. 20 g of Raney nickel, freshly prepared from a 50:50aluminium/nickel alloy, are added and hydrogen is injected toapproximately 40 bar. At a reaction temperature of 70°-75° C., thehydrogen pressure is kept within the range between 20 and 25 bar. Anadditional rise in pressure as the result of CO₂ being liberated shouldbe taken into account. When, after approximately 2-3 hours, theconsumption of hydrogen declines markedly, a sample is withdrawn andexamined by chromatography (silica gel on aluminium foil; eluant: 1:1acetone/ligroin) to check the completeness of dehalogenation. When thereaction is complete, the pressure in the autoclave is released, thelatter is flushed with nitrogen and the warm reaction mixture isclarified via a pressure filter, the catalyst being retained as aresidue on the filter.

The filtrate is concentrated on a rotary evaporator at 60° C./20 mm Hg.The resulting 263 g of an oil which contains sodium chloride and whichsolidifies in a crystalline state on cooling to 0°-5° C. prove tocontain virtually only the single substance 3-aminophenyl 2-hydroxyethylsulphone. According to determination of content, the product isapproximately 71% strength, which corresponds to a yield of 93% oftheory.

EXAMPLE 2

34.2 g of moist paste of 2-chloro-5-nitrophenyl 2-hydroxyethyl sulphonefrom Example 1 [or an equimolar amount of 4-chloro-3-nitrophenyl2-hydroxyethyl sulphone]are stirred into 250 ml of water and 50 ml of aphosphate buffer solution which has been prepared by dissolving 0.5 moleof disodium phosphate and 0.33 mole of monosodium phosphate in 1 l ofwater. When 1-2 g of a nonionic emulsifier and 1.5 g of Raney nickel,prepared from a 70:30 aluminium-nickel alloy, have been added, themixture is heated to 80° C. Hydrogen is then injected to 20 bar. Thesubsequent feed of hydrogen is controlled at such a rate that thepressure is constant at 10-15 bar. When the consumption of hydrogendeclines markedly, a sample is withdrawn and examined by chromatography(see Example 1) to check the completeness of the reduction. If, in agiven case, 5-amino-2-chlorophenyl 2-hydroxyethyl sulphone [or 3-amino-4-chlorophenyl 2-hydroxyethyl sulphone] is still detectable,approximately 0.5-1.0 g more catalyst is added and hydrogenation iscarried out again at 80° C. and 20 bar. When the reduction anddehalogenation are complete, the pressure in the autoclave is releasedand the latter is flushed with nitrogen, and the catalyst is removedfrom the warm reaction solution by suction filtration. The solution iscooled and acidified with hydrochloric acid, and the content of3-aminophenyl 2-hydroxyethyl sulphone in the solution is determined bydiazotization with 10% strength sodium nitrite solution. The yield isapproximately 90% of theory. The solution of 3-aminophenyl2-hydroxyethyl sulphone thus obtained can be processed further directlyin this form; it can, for example, be diazotized and the diazonium saltsolution can be coupled, as described in Japanese Patent Application No.05,667/70, with 7-acetylamino-1-naphthol-3-sulphonic acid.

EXAMPLE 3

102.6 g of moist paste of 2-chloro-5-nitrophenyl 2-hydroxyethyl sulphonefrom Example 1 [or an equimolar amount of 4-chloro-3-nitrophenyl2-hydoxyethyl sulphone] are stirred into 250 ml of water and 50 ml ofthe phosphate buffer solution described under Example 2. A small amountof a nonionic emulsifier and 5 g of palladium-oncharcoal catalyst areadded. Hydrogenation with hydrogen is then carried out in an autoclaveat 70° C. and approximately 40 bar. The reduction is monitored bychromatography. After the hydrogenation, and after releasing thepressure and flushing the reactor, the product is heated to 85° C. andclarified via a pressure filter. The filter is cooled to 0° C. and thecrystalline 3-aminophenyl 2-hydroxyethyl sulphone is isolated byfiltration. 53 g of single-substance product are obtained after drying.

I claim:
 1. A process for the preparation of the sulphone of the formula##STR3## wherein 2-chloro-5-nitrobenzenesulphochloride is reacted withsodium sulphite to give 2-chloro-5-nitrobenzenesulphinic acid, thebenzenesulphinic acid product is then reacted with ethylene oxide togive 2-chloro-5-nitrophenyl hydroxyethyl sulphone and the latter is thentreated with hydrogen in the presence of hydrogenation catalysts to formthe sulphone.
 2. Process according to claim 1 , whereinthe hydrogenationreaction is carried out in an aqueous or aqueous organic medium. 3.Process according to claim 1 , whereinthe hydrogenation reaction iscarried out at temperatures of about 40° to 120° C. and pH values of 5to
 8. 4. Process according to claim 1 , wherein the hydrogenationcatalysts used are nickel catalysts or Pd supported catalysts. 5.Process according to claim 4, wherein the metal catalyst is Raneynickel.